Histopathology

Carcinoid (well differentiated endocrine tumour)

The cells forming this tumour are uniform in size, with round or oval nuclei, inconspicuous nucleolus, and eosino-philic cytoplasm. Neoplastic cells are arranged in combined patterns with trabecular anastomosing structures, tubular structures and solid nests {1639, 299, 603, 177}. Tumour cells show positive staining for Grimelius silver {1639, 195, 115, 926, 1205}, chromogranin {1639, 57}, neuron-specific enolase {195, 115, 57}, and sev eral hormones including serotonin {115, 57}, gastrin {1175, 1156}, and somatostatin {603, 57}.

Cases showing regional or distant metastases {177, 926, 1205, 57} or signs of local aggressive growth, including invasion of the entire wall {1205, 57} and neural invasion {1205}, should be considered as well differentiated endocrine carcinomas (malignant carcinoids).

Small cell carcinoma (poorly differentiated endocrine carcinoma)

The cell population and growth patterns of this tumour are similar to those of small cell carcinoma of the lung {38, 40, 1359}. Small cell carcinomas appear to be more common in the gallbladder than in the extrahepatic bile ducts. Some mimic car-cinoid tumours.

Most tumours are composed of round or fusiform cells arranged in sheets, nests, cords, and festoons. Rosette-like structures and tubules are occasionally present. Extensive necrosis and subepithelial growth are constant features. In necrotic areas, intense basophilic staining of the blood vessels occurs. The tumour cells have round or ovoid hyperchromatic nuclei with inconspicuous nucleoli. A few tumour giant cells can be observed in some cases {1359, 34}. Occasionally, focal glandular configurations similar to

Fig. 9.22 Small cell carcinoma lying below normal gallbladder epithelium.

those of adenocarcinomas, and foci of squamous differentiation are seen {40, 774, 40, 1359}. Mitotic figures are frequently observed and they are reported to range from 15 to 206 (mean 75) per 10 high power fields {1359}. Most small cell carcinomas show scattered Grimelius positive cells. In addition, tumour cells immunoexpress epithelial markers such as EMA, AE1/AE3 and CEA, and endocrine markers such as NSE, chromogranin A, Leu7, serotonin, somatostatin, and ACTH {1359, 34}. Ultrastructurally, a small number of dense core secretory granules can be found {34, 37}.

Mixed endocrine-exocrine carcinoma

A significant number of cases reported in the older literature as carcinoids, includ ing the cases reviewed by Yamamoto et al. {2157}, are in fact mixed endocrine-exocrine carcinomas. These are composite tumours in which areas of adeno-carcinoma intermingle with areas of endocrine cell carcinoma formed by solid and/or trabecular structures with cells which are argyrophylic and immunoreactive for endocrine markers, including NSE, chromogranin, serotonin and gastrin {2157, 2030, 1405, 1575}. The adenocarcinoma component is usually tubular or papillary, formed by columnar cells, goblet cells and sometimes Paneth cells, but a case of a combined diffuse type tumour in which mucin-containing signet-ring cells were admixed with clear endocrine cells has also been reported {1455}. These tumours behave as adenocarcino-mas and, therefore, are clinically more aggressive than carcinoids. Adenocar-cinoma with endocrine cells should not be included in this category.

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